chr19-48219568-G-C

Position:

• chr19-48219568-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001184900.3(CARD8):​c.1162-556C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 151,938 control chromosomes in the GnomAD database, including 33,440 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.66 (33440 hom., cov: 31)
• Consequence: CARD8 NM_001184900.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27

Genes affected

CARD8 (HGNC:17057): (caspase recruitment domain family member 8) The protein encoded by this gene belongs to the caspase recruitment domain (CARD)-containing family of proteins, which are involved in pathways leading to activation of caspases or nuclear factor kappa-B (NFKB). This protein may be a component of the inflammasome, a protein complex that plays a role in the activation of proinflammatory caspases. It is thought that this protein acts as an adaptor molecule that negatively regulates NFKB activation, CASP1-dependent IL1B secretion, and apoptosis. Polymorphisms in this gene may be associated with a susceptibility to rheumatoid arthritis. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARD8	NM_001184900.3	c.1162-556C>G		intron_variant		ENST00000651546.1	NP_001171829.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARD8	ENST00000651546.1	c.1162-556C>G		intron_variant			NM_001184900.3	ENSP00000499211	A2

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100548 AN: 151820 Hom.: 33416 Cov.: 31

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.737

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.731

Gnomad SAS AF: 0.734

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.631

Gnomad OTH AF: 0.663

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.662 AC: 100623 AN: 151938 Hom.: 33440 Cov.: 31 AF XY: 0.665 AC XY: 49356 AN XY: 74216

Gnomad4 AFR AF: 0.711

Gnomad4 AMR AF: 0.668

Gnomad4 ASJ AF: 0.587

Gnomad4 EAS AF: 0.732

Gnomad4 SAS AF: 0.733

Gnomad4 FIN AF: 0.614

Gnomad4 NFE AF: 0.631

Gnomad4 OTH AF: 0.667

Alfa AF: 0.536 Hom.: 1487

Bravo AF: 0.666

Asia WGS AF: 0.757 AC: 2631 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.099
DANN	Benign	0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10418239; hg19: chr19-48722825;